Matthew Solomonson

Systematic common and rare variant association testing in 392,030 whole genomes in All of Us

The paper performs large-scale GWAS and RVAS on 392,030 whole genomes from All of Us, identifying 49,863 associations and 193 novel pLoF gene-phenotype links through meta-analysis with UK Biobank.

The Global Parkinson's Disease Genetics (GP2) Genome Browser

The paper introduces a genome browser for Parkinson's disease genomic data, integrating WGS and CES samples with variant annotations and ancestry stratification.

Integrating 730,947 exome sequences with clinical literature improves gene discovery

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

The landscape of regional missense mutational intolerance quantified from 730,947 exomes

The paper quantifies regional missense mutational intolerance using 730,947 exomes to identify constrained gene regions and improve variant interpretation.

Pan-UK Biobank GWAS improves discovery, analysis of genetic architecture, and resolution into ancestry-enriched effects

Meta-analyzing per-ancestry GWAS of 7,266 UK Biobank traits across six genetic ancestry groups adds 14,676 loci missed by European-only analysis, including ancestry-enriched CAMK2D and G6PD signals.

Inferring compound heterozygosity from large-scale exome sequencing data

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

Systematic single-variant and gene-based association testing of thousands of phenotypes in 426,370 UK Biobank exomes

The paper performs single-variant and gene-based association analyses of 4,529 phenotypes using exome data from 426,370 UK Biobank individuals, finding associations linked to variant frequency and deleteriousness.

Mapping the human genetic architecture of COVID-19: an update

This study updates the genetic architecture of COVID-19 by adding 11 new genome-wide significant loci through a large GWAS meta-analysis.

Exome sequencing identifies rare coding variants in 10 genes which confer substantial risk for schizophrenia

Exomes of 24,248 schizophrenia cases and 97,322 controls implicate ultra-rare damaging variants in 10 genes, including GRIN2A and GRIA3, with odds ratios of 3 to 50.

seqr: a web-based analysis and collaboration tool for rare disease genomics

seqr is a web-based tool for analyzing rare disease genomic data, enabling variant filtering, annotation, and collaboration, with over 10,000 families analyzed and 300 novel disease genes discovered.

Insights into genetic factors contributing to variability in SARS-CoV-2 susceptibility and COVID-19 disease severity

This study identifies genetic loci associated with SARS-CoV-2 susceptibility and disease severity using GWAS and colocalization, and links them to eQTLs in various tissues.

Ultra-rare constrained missense variants in the epilepsies: Shared and specific enrichment patterns in neuronal gene-sets

The paper analyzes ultra-rare variants in epilepsy patients to identify gene-set enrichment patterns and differential impacts in neuronal gene categories.

Exome sequencing in bipolar disorder reveals shared risk gene AKAP11 with schizophrenia

The paper reports exome sequencing findings in bipolar disorder, identifying AKAP11 as a shared risk gene with schizophrenia through ultra-rare protein-truncating variants.

Mapping the human genetic architecture of COVID-19 by worldwide meta-analysis

This study identifies 13 genome-wide significant loci associated with SARS-CoV-2 infection or severe COVID-19 through a global meta-analysis of 49,562 patients.

Evaluating potential drug targets through human loss-of-function genetic variation

The paper evaluates potential drug targets using loss-of-function genetic variants from gnomAD, highlighting the importance of deep curation and targeted recall studies for drug discovery.

The mutational constraint spectrum quantified from variation in 141,456 humans

From 125,748 exomes and 15,708 genomes, 443,769 high-confidence predicted loss-of-function variants yield LOEUF, a continuous gene intolerance score tracking mouse lethality, cell essentiality, and disease associations.

Transcript expression-aware annotation improves rare variant discovery and interpretation

The paper develops an expression-based annotation metric to improve rare variant interpretation by filtering false-positive loss-of-function variants and identifying pathogenic variants in highly expressed exons.

An open resource of structural variation for medical and population genetics

Short-read genome sequencing of 14,891 diverse genomes yields 433,371 structural variants (SVs) for gnomAD; loss-constrained genes also resist duplication, and clinical SV carrier rates are benchmarked.

Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinsons disease

The paper analyzes loss-of-function variants in LRRK2 across large genomic datasets to assess the safety of partial LRRK2 inhibition as a Parkinson's disease therapy.

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

The paper systematically studies uORF variants in 15,708 genomes, showing they are under strong negative selection and contribute to disease.

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

Ultra-rare genetic variation in the epilepsies: a whole-exome sequencing study of 17,606 individuals

This study identifies ultra-rare genetic variants associated with different epilepsy types using whole-exome sequencing in 17,634 individuals.